The proposed experiments are designed to aid in elucidating the significance of cyclic GMP and related metabolic components in biological communication and regulation. Major effort focuses on the mechanism by which guanylate cyclase activity is regulated with emphasis on the oxidative-reductive mode of modulation by hydrophilic and hydrophobic ligands which include substances such as ascorbic acid and fatty acid hydroperoxides and endoperoxides. The chemical alteration induced by oxidants and reductants will be studied with purified guanylate cyclases from human platelets, lymphocytes and rat splenic cells. Kinetic parameters and cation requirements altered as a result of oxidation or reduction will also be examined.